POS0110 INCIDENCE OF MAJOR ADVERSE CARDIOVASCULAR EVENTS STRATIFIED BY GEOGRAPHIC REGION AND BASELINE CARDIOVASCULAR RISK: A POST HOC ANALYSIS OF ORAL SURVEILLANCE
Authors: Z. Szekanecz, J. T. Giles, M. H. Buch, S. R. Ytterberg, M. Dougados, D. L. Bhatt, G. G. Koch, I. Vranic, J. Wu, C. Wang, K. Kwok, S. Menon, J. L. Rivas, A. Yndestad, C. A. Connell, C. Charles-Schoeman
Journal: Annals of the Rheumatic Diseases (2022)

Background ORAL Surveillance was a post-authorisation safety study of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in patients (pts) with rheumatoid arthritis (RA) aged ≥50 yrs with ≥1 additional cardiovascular (CV) risk factor and an inadequate response to methotrexate (MTX). Objectives To examine associations between major adverse CV events (MACE) and the geographic region and baseline (BL) CV risk profile of pts in ORAL Surveillance. Methods Pts on stable MTX were randomised 1:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID) or a TNFi (adalimumab 40 mg every 2 weeks in North America [NA] or etanercept 50 mg once weekly in the rest of the world [RoW]). Incidence rates (IRs; pts with first events/100 pt-yrs) were evaluated for adjudicated MACE, as well as myocardial infarction (MI) and stroke. MACE was defined as CV death (excluding CV death due to pulmonary embolism), non-fatal MI and non-fatal stroke. IRs were stratified by geographic region (NA vs RoW) and BL CV risk profile: pts were first categorised by history of coronary artery disease (HxCAD); pts without a HxCAD were then categorised by 10-yr risk of MACE (high [≥20%], intermediate [≥7.5–&lt;20%], borderline [≥5–&lt;7.5%] and low [&lt;5%] risk), per the ASCVD-pooled cohort equations calculator 1 with a 1.5 multiplier applied. 2 Results Overall, 4362 pts were included in the study (tofacitinib 5 mg BID, n=1455; tofacitinib 10 mg BID, n=1456; TNFi, n=1451). Across treatments, a higher proportion of pts in NA vs RoW had a HxCAD (Table 1). In pts without a HxCAD, across treatments, higher percentages of pts had a high 10-yr risk of MACE in NA vs RoW (Table 1). Across treatments, overall MACE IRs were higher in pts in NA vs RoW (Figure 1). Incidence and risk of MACE were higher with tofacitinib vs TNFi in both NA and RoW (Figure 1). In NA, MACE IRs were higher for tofacitinib 5 mg BID vs TNFi in pts with a HxCAD, and tofacitinib 10 mg BID vs TNFi for pts with a high 10-yr risk of MACE; pts with low or borderline 10-yr MACE risk had no MACE across tofacitinib groups (Figure 1). Compared with NA, similar trends for MACE were generally observed across treatments in RoW, particularly for intermediate, borderline and low CV risk categories (Figure 1). Table 1. Percentages of pts in NA and RoW with a HxCAD and pts without a HxCAD categorised by 10-yr risk of MACE, per ASCVD-pooled cohorts equation risk calculator 1 with a 1.5 multiplier applied 2 NA a RoW Tofacitinib 5 mg BID (N=402) Tofacitinib 10 mg BID (N=409) TNFi b (N=432) Tofacitinib 5 mg BID (N=1053) Tofacitinib 10 mg BID (N=1047) TNFi b (N=1019) HxCAD, n (% ) 58 (14.4) 64 (15.6) 81 (18.8) 103 (9.8) 108 (10.3) 83 (8.1) No HxCAD: 10-yr risk of MACE, n (% ) High (≥20%) 97 (24.1) 108 (26.4) 113 (26.2) 177 (16.8) 195 (18.6) 183 (18.0) Intermediate (≥7.5–&lt;20%) 131 (32.6) 144 (35.2) 137 (31.7) 359 (34.1) 372 (35.5) 368 (36.1) Borderline (≥5–&lt;7.5%) 49 (12.2) 31 (7.6) 31 (7.2) 151 (14.3) 143 (13.7) 124 (12.2) Low (&lt;5%) 60 (14.9) 54 (13.2) 65 (15.0) 253 (24.0) 218 (20.8) 250 (24.5) Missing data 7 (1.7) 8 (2.0) 5 (1.2) 10 (0.9) 11 (1.1) 11 (1.1) HxCAD was defined as any history of MI, coronary heart disease, stable angina pectoris or coronary artery procedures . a United States, Puerto Rico and Canada . b For pts randomised to the TNFi group, adalimumab and etanercept were administered in NA and RoW, respectively n, number of pts with specified characteristics; N, number of evaluable pts Conclusion This post hoc analysis of data from ORAL Surveillance suggests that differences in MACE IRs across geographic regions are largely driven by HxCAD and high BL CV risk scores in NA vs RoW. Results should be interpreted with caution due to low pt and event numbers, particularly restricting the evaluation of tofacitinib vs TNFi in NA and RoW. Noting this limitation, these findings emphasise the importance of assessing and addressing BL CV risk when treating pts with RA. References [1]American College of Cardiology, American Heart Association. ASCVD risk estimator. https://tools.acc.org/ldl/ascvd_risk_estimator/index.html#!/calulate/estimator/ . [2]Agca et al. Ann Rheum Dis 2017; 76: 17-28. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by Tanya Guha, CMC Connect, and funded by Pfizer Inc. Disclosure of Interests Zoltán Szekanecz Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer Inc, Roche and Sanofi, Paid instructor for: AbbVie, Eli Lilly, Gedeon Richter, Novartis, Pfizer Inc and Roche, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer Inc, Roche and Sanofi, Grant/research support from: Pfizer Inc, Jon T Giles Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Genentech, Gilead Sciences and UCB, Grant/research support from: Pfizer Inc, Maya H Buch Speakers bureau: AbbVie, Consultant of: AbbVie, Eli Lilly, Gilead Sciences, MSD, Pfizer Inc and Roche, Grant/research support from: Pfizer Inc, Roche and UCB, Steven R. Ytterberg Consultant of: Corbus Pharmaceuticals, Kezar Life Sciences and Pfizer Inc, Maxime Dougados Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche and UCB, Deepak L Bhatt Grant/research support from: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Lexicon, Eli Lilly, Medtronic, MyoKardia, Novo Nordisk, Owkin, Pfizer Inc, PhaseBio, PLx Pharma, Regeneron, Roche, Sanofi, Synaptic and The Medicines Company, Gary G Koch Shareholder of: IQVIA, Grant/research support from: AbbVie, Acceleron, Amgen, Arena, AstraZeneca, Cytokinetics, Eli Lilly, Gilead Sciences, GSK, Huya Bioscience International, Johnson &amp; Johnson, Landos Biopharma, Merck, Momentum, Novartis, Otsuka, Pfizer Inc, Sanofi and vTv Therapeutics, Employee of: University of North Carolina at Chapel Hill, Ivana Vranic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cunshan Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Kenneth Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Sujatha Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose L. Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer SLU, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Carol A. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Christina Charles-Schoeman Consultant of: AbbVie, Gilead Sciences, Pfizer Inc and Sanofi-Regeneron, Grant/research support from: AbbVie, Bristol-Myers Squibb and Pfizer Inc